2-Aryloxy- and 2-alkoxy-6-ethylnaphthalene compounds are useful as intermediates for the preparation of other organic compounds. For example, we have determined that 2-methoxy-6-ethylnaphthalene, a 2-alkoxy-6-ethylnaphthalene compound, is an intermediate suitable for the synthesis of (s)-6-methoxy-.alpha.-methyl-2-naphthaleneacetic acid, also known as d-2-(6-methoxy-2-naphthyl) propionic acid, and commonly referred to as Naproxen. Naproxen is an analgesic and anti-inflammatory agent. The structure of 2-(6-methoxy-2-naphthyl) propionic acid, i.e. the racemic compound, is as follows: ##STR1##
However, heretofore known methods for preparing 2-methoxy-6-ethylnaphthalene are complicated and, therefore, undesirable for large-scale manufacturing processes. For example, 2-methoxy-6-ethylnaphthalene has been prepared by acetylating 2-methoxynaphthalene in the usual Friedel-Crafts manner using a stoichiometric amount of Friedel-Crafts catalyst to form 2-methoxy-6-acetylnaphthalene. However, the yield of the 2,6-product was reported to be about 35 percent and it was difficult to separate the desired 2-methoxy-6-acetylnaphthalene from the 2-methoxy-1-acetylnaphthalene that was also produced in the reaction. Furthermore, in order to prepare 2-methoxy-6-ethylnaphthalene an additional step was required wherein the acetyl moiety on the 2-methoxy-6-acetynaphthalene molecule was reduced to an ethyl moiety using a Clemmensen reduction procedure.
The art therefore needs an improved method for the production of 2-aryloxy- or 2-alkoxynaphthalenes and, in particular, the art needs an improved method for the preparation of 2-methoxy-6-ethylnaphthalene. The present invention provides such an improved method. Also, although Naproxen contains a methoxy group, it is possible that the substitution of the methoxy group with an aryloxy or other alkoxy group may provide for compositions also having analgesic and/or anti-inflammatory activity. The present invention makes possible a simplified preparation of these compositions by making available the 2-aryloxy- and 2-alkoxy-6-ethylnaphthalene starting materials.